CONGENITAL MYASTHENIC SYNDROMES

Objectives: To summarize the current knowledge of congenital myasthenic syndromes (CMS), the approach to diagnosis and review our series.

Methods: CMS are a heterogeneous group of disorders caused by genetic defects affecting neuromuscular transmission. The progress of molecular genetic has changed and made easier their diagnosis, that is based on several steps 1) Clinical suspicion, not always easy. In most cases congenital ptosis, ophtalmoplegia, bulbar and respiratory muscular involvement, and fatigability give the clue. However, other patients suffer non-specific and generalized myopathic symptoms, without fatigability, or their onset is later in life. 2) EMG study must include repetitive nerve stimulation at low and high frequencies. In most cases, but not all, EMG shows decrement of amplitude of 4° potential. 3) Even without specific clinical-EMG signs, CMS must be suspected in case of severe congenital muscular involvement with only slight, non-specific results in EMG or biopsy. 4) Response to treatment with anticholinesterase drugs, with 3,4-diaminopyridine, or combination of both. But not all CMS improve with them. 5) Molecular genetic studies, which now avoids muscular biopsy in most cases. 6) Biopsy with histologic-histochemical studies of neuromuscular transmission.

Results: CMS classification is based on the type of transmission anomaly: 1) Presynaptic, usually caused by mutations of cholineacetyltransferase gene, CHAT, 2) Synaptic, caused by deficiency of acetylcholinesterase produced by mutation of the collagen tail of the gene, COLQ. 3) Postsynaptic, usually caused by mutations of subunits of acetylcholine receptor (CHRNA1, CHRNB1, CHRND, CHRNE) or by mutation of rapsyn gene (RAPSN). Other less characterized CMS are described. In the reported series, as in our institution, postsynaptic CMS are the commonest of all. Our series results are presented.

Conclusion: CMS are commoner than reported, and its early diagnosis is crucial in order to prevent severe complications, even death, because many of them respond to drugs.